PROJECT SUMMARY Aphasia affects approximately one-third of stroke survivors and persists in about 15% of these individuals, resulting in debilitating, life-long impairments in functional communication and severely diminished quality of life. Research has shown that despite persistent deficits, persons with chronic aphasia (PWA) can demonstrate improved language skills with concomitant neurophysiological changes following language therapy. However, response to treatment is variable and there is currently no way to predict the degree to which PWA may recover. One reason for the difficulty in predicting aphasia outcomes is that the mechanisms of beneficial neural reorganization of language are unclear. Specifically, optimal language recovery has been linked to activation in left hemisphere (LH) tissue, yet the specific regions that drive improved performance and the cognitive functions they mediate (i.e., language-specific versus domain-general processes) are unknown. Even less is understood regarding the role of the right hemisphere (RH) in reorganization. Some evidence suggests RH activity for language is maladaptive while other findings indicate RH recruitment is essential when LH lesions are large or when aphasia is severe. This traditional LH versus RH debate appears to oversimplify a complex problem. The alternative, central hypothesis of the proposed research is that language reorganization involves the dynamic recruitment of intact tissue within a bilateral network of anatomically-segregated but functionally and structurally connected language-specific and domain-general brain regions. This hypothesis will be tested through two specific aims. First, effective connectivity (which reflects the causal influence of activated regions on other areas) of a bilateral brain network for two related language tasks (i.e., picture naming and semantic feature verification) will be examined via Dynamic Causal Modeling (DCM) in 45 PWA and 35 age-matched controls. We will test the hypothesis that the most active hubs and modulatory regions for both tasks will be domain-general left middle frontal gyrus (LMFG) for PWA and language-specific left inferior frontal gyrus (LIFG) for controls and that best-fit brain models for PWA will include stronger inter-hemispheric interactions than best- fit models in controls. Second, we will examine the extent to which PWAs? language network structural integrity and task-based connectivity predict their language abilities. We will test the hypothesis that greater effective and structural connectivity of anterior regions within the bilateral network predict better language abilities while stronger connectivity of only intra-RH connections will be predictive of poor performance. By achieving these aims, this project will advance our understanding of the nature of beneficial neural reorganization of language in stroke-induced chronic aphasia. Ultimately, such findings can be incorporated into future work to improve our prognostication of long-term recovery and response to therapy in PWA.